Name: Intracortical Inhibition Within the Primary Motor Cortex Can Be Modulated by Changing the Focus of Attention (Video) | JoVE Journal
Uploaded: 2017-09-11T12:30:00.000+00:00
Duration: 9 min 48 s
Description: Learn how to use transcranial magnetic stimulation to investigate intracortical inhibition in the primary motor cortex during motor tasks with different attentional foci. This protocol reveals neural mechanisms underlying attention effects.

ai_agent_IP

ai_agent

maintenance

instantTrialDurationMinutes

isBiopharma

enableNewMyJoveSectionDesign

educationFeatures

seoMetaApi

ai_copilot_institution_blacklist

ai_chat_institution_blacklist

freeAccessWindow

ssoRoleCapture

scheduledMaintenanceBanner

joveLabsFeatures

disable_autoplay_for_bots

extended_trial_duration

5 minutes

The authors have no acknowledgements.

This protocol was approved by the local ethics committee, and the experiments are in accordance with the Declaration of Helsinki (1964).
1. Ethical Approval and Subject Instruction
<ol>
	<li>Before starting the measurement, instruct all participants about the potential risk factors and the purpose of the study. Do not give information about the attentional foci, as this might affect the results. Ensure that the safety guidelines for the application of TMS in research settings 30 are followed. 
	NOTE: When applying TMS, there are some medical risk factors, including implanted cranial electrodes and cochlear implants, personal history of syncope or seizure, epilepsy, cerebral lesion, drug/medication interactions, recent drug withdrawal, pregnancy, or illness. TMS should not be administered in children.</li>
	<li>In the study, include healthy participants (n = 14) between 18 and 35 years old. Exclude subjects with any orthopedic and/or neurological/mental diseases. Ensure that all participants are right-handed.</li>
</ol>
2. Experimental Design and Setup
<ol>
	<li>Divide the group in two. Instruct one half of the group on IF instructions first, followed by EF instructions in the second experimental session (see section 4.2.2 for the verbal instructions). Instruct the other half in a counterbalanced order. 
	NOTE: The experiment consists of a total of four laboratory sessions (see Figure 1) that must be separated by a minimum of 72 h. The first two sessions consist of measuring the maximal force (Fmax) and the TTF of submaximal sustained index finger abduction (see step 4). The third and fourth sessions consist of measuring the activity of inhibitory circuits within the M1 during the task by means of subTMS and ppTMS (see Figure 1).</li>
</ol>
3. Subject Preparation
<ol>
	<li>Seat the participant in an adjustable and comfortable chair throughout the whole experiment. Place a monitor 1 m in front of the participant.</li>
	<li>Place the left arm in a comfortable and relaxed position under the table, resting on the left leg. If needed, adjust the position of the arm with a pillow. Place the right arm of the subject in a custom-built splint in pronated position (see Figure 2). 
	NOTE: Here, the splint is made of thermoplastic and fit all participants (for details, see16). In addition, the splint was conceived to restrict the degrees of freedom of the wrist joint (see Figure 2B). The only movements allowed were the abduction and adduction of the metacarpophalangeal joint of the index finger of the right hand.</li>
	<li>Align the finger joint with the axis of rotation of the custom-made device. Once the optimal position is found, record manually and take a picture of the antero-posterior and medio-lateral positions of the splint to use comparable positions in sessions 2, 3, and 4.</li>
</ol>
4. Sessions 1 and 2: Behavioral Tests
<ol>
	<li>Maximal isometric contractions (see Figure 1A).
	<ol>
		<li>Align the axes of rotation of the goniometer and the metacarpophalangeal joint and fix the goniometer properly using screws (see Figure 2). Place the force transducer in a way that allows for maximum voluntary contractions (see Figure 2B).</li>
		<li>Connect the EMG cable (FDI muscle), the force transducer, and the goniometer cables to the appropriate amplifier and/or analog to digital (A-D) converter.</li>
		<li>Have the participant perform 3 maximal isometric abductions of the index finger, with a 30-s break between each contraction, and determine the Fmax. 
		NOTE: The Fmax is determined as the highest peak in the force signal obtained from the force transducer. Explain to the participant that maximal contractions consist of a gradual increase in force from 0 N to the individual maximum. Importantly, instruct participants to perform an isometric contraction against the stationary force transducer. Participants should abduct the index finger at the metacarpophalangeal joint and push as hard as possible against the force transducer. A 3-s time span should be given per contraction, and participants should be instructed to sustain the maximal force for 2 s16,25,26. Between each contraction, give the participants a 30-s break.</li>
		<li>Have the subject push the lever against the force transducer, without giving any instruction about the focus of attention. 
		NOTE: The same task will be done at the beginning of session 2 to ensure that the Fmax and the position in the splint have not changed between sessions.</li>
		<li>After maximal contractions, remove the force transducer, allowing the index finger to move freely in the transverse plane (abduction/adduction).</li>
		<li>Calculate the Fmax from the maximal isometric abductions (step 4.1.3) using the raw data on the computer. Determine 30% (Fmax * 0.3; sessions 1 and 2) and 10% (Fmax * 0.1; sessions 3 and 4) of Fmax. 
		NOTE: Consider the Fmax as the highest peak found in the force signal obtained from the force transducer. In the following sessions, the different contraction intensities (30% and 10%) will be calculated from the Fmax obtained at this stage of the experiment.</li>
		<li>Fill a bottle of water to the amount representing the 30% of Fmax obtained from step 4.1.6. Attach the weight of Fmax to the rope of the device (see Figure 2A). 
		NOTE: The volumetric mass density of water is 1 kg/L. Thus, if the 30% of Fmax of one participant represents 0.4 kg, adjust the weight of the bottle to the equivalent of 0.4 kg.</li>
	</ol>
	</li>
	<li>Sustained contractions until TTF (see Figure 1A).
	<ol>
		<li>Instruct the participants about the task. 
		NOTE: Participants must hold the finger in the target position by counteracting the weight (see Figure 2), performing an abduction of the index finger. The task must be performed until task failure. The task failure is determined as a deviation greater than 10 degrees from the target position. The deviation is measured by the goniometer and displayed on the monitor (see Figure 2B).</li>
		<li>Randomize the order of session (see step 2.1; EF or IF condition). Verbally instruct the participants on the adequate condition (IF or EF).
		<ol>
			<li>For the EF condition, instruct as follows: &#34;Concentrate on the position of the goniometer. Hold this position as long as possible. When the position of the goniometer changes, the thickness of the red line on the screen changes. Correct the position of the goniometer until the red line is thin again.&#34; Instruct the participant to &#34;control and concentrate on the position of the goniometer&#34; every 30 s.</li>
			<li>For the IF condition, instruct as follows: &#34;Concentrate on the position of your finger. Hold this position as long as possible. When the position of your finger changes, the thickness of the red line on the screen changes. Correct the position of your finger until the red line is thin again.&#34; Instruct the participant to &#34;contract and concentrate on his finger muscles&#34; every 30 s.</li>
		</ol>
		</li>
		<li>Have the participants hold the finger in the target position by counteracting the weight (see Figure 2), performing an abduction of the index finger. Have them perform the task until task failure.</li>
		<li>Press the &#34;record&#34; button on the recording software to start recording the goniometer signal and wait until task failure. Once task failure is reached, press the &#34;stop recording&#34; button on the recording software to stop the recording and save the goniometer signal on the computer. Remove the participant&#39;s hand from the orthopedic splint; the first session is now over.</li>
		<li>Respecting the minimum inter-session period (72 h), repeat steps 4.2.1-4.2.4. In addition, allow a minimum of a 72-h break between sessions 2 and 3 and sessions 3 and 4.</li>
	</ol>
	</li>
</ol>
5. Sessions 3 and 4: Brain Stimulation
<ol>
	<li>Surface electromyography (sEMG) recordings.
	<ol>
		<li>Shave the hair on the skin over the right FDI muscle, if needed, and then slightly abrade the skin using abrading gel. Disinfect the abraded area with a solution containing 80% ethanol and 1% glycerin. Allow the ethanol to evaporate.</li>
		<li>Place the Ag/AgCl bipolar surface electrodes in a belly-tendon montage on the FDI, with 1-cm interelectrode distance. Place the reference electrode on the phalanx of the digitus medius.</li>
		<li>Connect the EMG cable (FDI muscle) and the goniometer cable to an EMG amplifier and to an A-D converter.</li>
		<li>Use Ag/AgCl bipolar surface electrodes to record and measure muscular activity and electrophysiological responses elicited by brain stimulation from the FDI muscle. 
		NOTE: For the final analysis (subTMS-induced EMG suppression and peak-to-peak MEP amplitude), the EMG signal (from the FDI) must be adjusted as follows: amplification of x1000, Butterworth band-pass filtering of 10-1000 Hz, and sampling of 4 kHz. Store all EMG data on a computer for offline analysis.</li>
	</ol>
	</li>
	<li>Repeat steps 3.1 and 3.2.</li>
	<li>Transcranial magnetic stimulation
	<ol>
		<li>Fix the reflective markers on the participant&#39;s forehead with double-sided adhesive tape. 
		NOTE: Reflective markers allow for the constantly delivery of TMS to the target area over M1 by using a neuronavigation system (see Figure 2). The advantage of the neuronavigation system is that the coil position can be recorded relative to the skull position in space and be checked at any time throughout the entire experiment.</li>
		<li>Use a 95-mm focal figure of eight coils attached to a TMS stimulator to deliver stimuli to the contralateral motor cortical hand area. 
		NOTE: Check that the stimulator allows for paired-pulse stimulation paradigms (session 4). In addition, the induced current must be directed posterior to anterior and must be delivered in reverse mode. The wave form should be monophasic.</li>
		<li>Find the optimal position (hot spot) of the coil relative to the skull for eliciting motor evoked potentials (MEPs) in the FDI muscle by performing a classical mapping procedure.
		<ol>
			<li>Start by placing the coil approximately 0.5 cm anterior to the vertex and over the midline, with the coil handle pointing at 45&#176; towards the contralateral forehead. 
			NOTE: This will ensure that the induced current flow is approximately perpendicular to the central sulcus31.</li>
			<li>To get the participants used to the TMS stimuli, start at intensities below 25% of maximum stimulator output (MSO). Then, start to increase the stimulation intensity and move the coil in the medio-lateral and rostro-frontal direction to discover the hot spot.</li>
		</ol>
		</li>
		<li>Once the hot spot is found, record the optimal position with the neuronavigation system.Determine the active motor threshold (aMT) by adjusting the intensity of the stimulator output. Define the aMT as the minimum intensity required to evoke MEP peak-to-peak amplitudes in the EMG of the FDI larger than 0.1 mV in three out of five consecutive trials21.</li>
	</ol>
	</li>
	<li>Session 3: SubTMS-induced EMG suppression (see Figure 1B).
	<ol>
		<li>Prepare the weight representing the 10% of Fmax by filling the bottle of water (see step 4.1.7). 
		NOTE: The 10% of Fmax are selected based on the Fmax (the best of 3 trials) performed in step 4.1.3. In the subthreshold TMS protocol, only 10% of the Fmax has to be selected, as it has previously been shown that fatigue has an influence on subTMS-induced EMG suppression32,33. For the same reason, the subTMS session must be carried out on a separate session. The volume of water used here is between 0.3 L (smallest 30% of Fmax) and 1.2 L (biggest 30% of Fmax).</li>
		<li>Instruct participants about the task; the motor task consists of holding the index finger in the target position by counteracting the light weight of 10% (abduction of the index finger; the same task as in sessions 1 and 2, but with less weight).</li>
		<li>As the participants remain relaxed in a comfortable position, find the optimal intensity for eliciting subTMS-EMG suppression, without giving any instruction about the focus of attention. To do this, successively diminish in steps of 2% MSO from the aMT determined previously.</li>
		<li>While they are still seated in the relaxed and comfortable position, have the participants perform two separate isometric index finger abductions at 10% of Fmax and record the EMG signal of the FDI. During this isometric index finger abduction, record (by pressing the &#34;record&#34; button on the recording software) 20 trials with and 20 trials without TMS, with a randomized interstimulus interval (ISIs) ranging from 0.8 to 1.1 s16,25,26,33,34 in a 100-ms time window. 
		NOTE: This interval ensures that participants do not have to perform the motor task for too long and therefore minimizes fatiguing effects. After each series, check the subTMS-induced EMG suppression.
		<ol>
			<li>Apply a full-wave rectification by converting all negative amplitudes to positive amplitudes in the EMG signals. Average the EMG signals using time-normalized averaging35. 
			NOTE: The onset of subTMS-EMG suppression is defined as the moment when the difference between the trials with and those without TMS is negative for at least 4 ms in a time window from 20 to 50 ms after the TMS: EMGDiff = EMGWithout- EMGWith.</li>
		</ol>
		</li>
		<li>Repeat step 5.4.3 until the optimal stimulation intensity is found, indicated by the largest EMG suppression. 
		NOTE: The optimal intensity is found at around 80% of aMT16.</li>
		<li>Give the participant the adequate instructions (see step 4.2.2) regarding the condition (IF or EF). Repeat the instructions before each series (step 4.2.2).</li>
		<li>While they remain seated in the relaxed and comfortable position, have the participants perform four separate isometric index finger abductions (2 times with each focus: EF and IF) at 10% of Fmax and record the EMG signal of the FDI.
		<ol>
			<li>During this isometric index finger abduction, record (by pressing the &#34;record&#34; button on the recording software) 40 trials with and 40 trials without TMS, with randomized ISIs for each condition (i.e., IF and EF) in a counterbalanced order. Use the same intensity for each condition (determined in point 5.4.5).</li>
		</ol>
		</li>
		<li>Between each series, allow a break of a minimum of 5 min to minimize any bias that may be induced by fatigue.</li>
	</ol>
	</li>
	<li>Session 4: ppTMS (see Figure 1B). 
	NOTE: The paired-pulse paradigm is composed of a conditioning stimulus at 0.8 aMT, followed by a suprathreshold control stimulus at 1.2 aMT.
	<ol>
		<li>Repeat steps 5.1-5.4. In brief, place EMG electrodes over the FDI muscle, seat the participant in an adjustable and comfortable chair, and place the left arm in a comfortable and relaxed position under the table (i.e., on the left leg). Find the hotspot for TMS over the M1.</li>
		<li>Set the intensity on the stimulator, the ISI at 2.5 ms36, and the interval between paired and single-pulse TMS at 0.25 Hz.</li>
		<li>Give the participant adequate instructions (see step 4.2.2) regarding the condition (i.e. IF or EF). Repeat the instructions before each series.</li>
		<li>Have the participants perform four separate isometric index finger abductions (2 times with each focus: EF and IF) at 10% of Fmax and record the EMG signal of the FDI. During the isometric contraction, record 20 TMS stimuli for each condition (i.e., IF and EF) in a counterbalanced order. 
		NOTE: One set of 20 stimuli must be composed of 10 conditioned MEPs (paired-pulse at 0.8-1.2 aMT) and 10 control MEPs (single-pulse at 1.2 aMT). Use the same intensity for each condition (determined in step 5.5.2).</li>
		<li>Between each series, allow a break of a minimum of 5 min to minimize any bias that may be induced by fatigue.</li>
	</ol>
	</li>
</ol>
6. Data Processing and Analysis
<ol>
	<li>SubTMS.
	<ol>
		<li>As explained above (step 5.1.1.3), rectify and average the EMG for analysis.</li>
		<li>Detect the onset of subTMS-EMG suppression (see Figure 4). 
		NOTE: It is defined as the moment when the difference between the average of all trials with and those without TMS is negative for at least 4 ms in a time window from 20-50 ms after the TMS.</li>
		<li>To detect the end of subTMS-EMG suppression, define the moment after the onset of suppression (step 6.1.2) when the difference between the average of all trials with and those without TMS is positive again for at least 4 ms (see Figure 4a).</li>
		<li>Calculate the subTMS-induced EMG as follows: 
		EMGDiff = EMGWithout &#8211; EMGWith.
		<ol>
			<li>Compute the cumulative trapezoidal numerical integration from the onset to the end of the suppression to quantify the amount of subTMS-induced EMG suppression.</li>
		</ol>
		</li>
	</ol>
	</li>
	<li>ppTMS.
	<ol>
		<li>Use the following formula to express the magnitude of SICI as a percentage relating to the control MEP: 
		100 &#8211; (conditioned MEP/control MEP &#215; 100).
		<ol>
			<li>Use the results as percentage values for the final analysis.</li>
		</ol>
		</li>
		<li>Calculate peak-to-peak MEP amplitudes (in mV; in the EF and IF conditions) and compare the two conditions in the final analysis.</li>
	</ol>
	</li>
	<li>EMG.
	<ol>
		<li>As background EMG has an influence on the magnitude of MEPs37, determine the EMG activity by computing the root-mean-square value in a 100-ms window before the TMS.</li>
	</ol>
	</li>
</ol>

The authors have nothing to disclose.

This protocol shows two possible methods to investigate the activity of inhibitory circuits within the M1 using TMS. More precisely, these two protocols have been used in this study to investigate the impact of attentional foci on the activity of inhibitory circuits within the M1.
One limitation of the presented method is that it is not always possible to cause a subTMS-induced EMG suppression without a facilitation preceding it. In this study, for example, four subjects had to be removed from...

It is now generally accepted that adopting an EF compared to an IF or neutral focus of attention promotes motor performance and learning in numerous settings1. It has been shown, for example, that adopting an EF leads to benefits in accuracy2,3, balance4,5,6, force production7,8, jumping performance7,9,10,11, movement speed12, oxygen consumption13,14, and fatiguing tasks15,16.
On the other side, since brain activation is the basis of all movements, several aspects of the neural control of movement have been investigated. For example, the level and the ability to modulate intracortical inhibition within the M1 has been shown to have a strong influence on motor function, such as interlimb coordination17, postural control18, and dexterity19. Furthermore, populations with poorer motor control abilities than young adults, such as elderly subjects or children (born preterm20), usually show less pronounced inhibitory control. Thus, although the role of inhibitory processes is not yet well understood, inhibitory processes nevertheless seem to be important to the quality of motor execution in general.
A possibility to investigate intracortical inhibitory circuitries is to use non-invasive transcranial magnetic stimulation (TMS). The most commonly used stimulation protocol applies paired-pulse TMS (ppTMS) to induce SICI. This protocol uses a conditioning stimulus below the motor threshold to reduce the amplitude of the suprathreshold control stimulus response elicited at an interstimulus interval of 1-5 ms21,22,23,24. Then, reported as the percentage of the control stimulus, the amplitudes of the motor-evoked potentials (MEPs) can be compared across conditions, giving information about cortical inhibitory activity and modulation within the M1.
Another stimulation protocol to assess the activity of intractortical inhibitory circuits applies single pulses, where all stimuli are delivered at intensities below the motor threshold (i.e., subTMS). This protocol induces suppression in the ongoing EMG activity18,25,26. This so-called subTMS-induced EMG suppression can be compared in terms of amount and duration. Although this protocol is not so commonly used, it has certain advantages compared to the standard SICI protocol. This protocol does not disturb motor execution, as it does not induce suprathreshold stimuli. Both methods test the responsiveness of intracortical gamma-aminobutyric acid (GABA) inhibitory interneurons23,27.
Despite the well-known benefits of using an EF compared to an IF on motor performance1, the underlying neural processes remain largely unknown. In a former fMRI study28, it was shown that blood-oxygen level-dependent (BOLD) activation was enhanced in the M1, primary somatosensory, and insular cortices when subjects executed a finger sequence and adopted an EF compared to an IF. As excitatory and inhibitory activity cannot be differentiated by fMRI29, another recent study16 stipulated that the enhanced activity in the M1 associated with an EF could, in fact, be due to the enhanced activity of intracortical inhibitory circuits. More precisely, this study showed that the excitability of inhibitory GABAergic neurons can be modulated instantly by the type of attentional focus adopted in one and the same person.
The main aim of the present protocol is to show two possible ways to compare the immediate effects of cognitive manipulation (i.e., focus of attention instructions) on the activity of intracortical inhibitory circuits within the M1. SubTMS and ppTMS are both used. In addition, this protocol shows one possible way to explore the influence of attentional foci on motor behavior in a very controlled way by investigating the TTF of submaximal isometric sustained contraction of the FDI.

<table><tbody><tr><td>MC3A-100</td><td>Advanced Mechanical Technologies Inc., Watertown, MA, USA</td><td>-</td><td>Force transducer</td></tr><tr><td>BlueSensor P</td><td>Ambu A/S, Bellerup, Denmark</td><td>-</td><td>Ag/AgCl surface electrodes for EMG</td></tr><tr><td>Polaris Spectra</td><td>Northern Digital, Waterloo, ON, Canada</td><td>-</td><td>neuronavigation system, active or passive markers tracker</td></tr><tr><td>Localite TMS Navigator Version 2.0.5</td><td>LOCALITE GmbH, Sankt Augustin, Germany</td><td>-</td><td>navigation system for transcranial magnetic stimulation (TMS)</td></tr><tr><td>MagVenture MagPro X100</td><td>MagVenture A/S, Farum, Denmark</td><td>9016E0711</td><td>Transcranial magnetic stimulator</td></tr><tr><td>MagVenture D-B80</td><td>MagVenture A/S, Farum, Denmark</td><td>9016E0431</td><td>TMS coil (figure of eight)</td></tr><tr><td>Goniometer</td><td>N/A</td><td>-</td><td>Custom-made goniometer</td></tr><tr><td>Othopedic splint</td><td>N/A</td><td>-</td><td>Custom-made splint</td></tr><tr><td>Recording software</td><td>LabView based</td><td>-</td><td>Custom-made script</td></tr></tbody></table>

intracortical inhibition within the primary motor cortex can be modulated by changing the focus of attention

Intracortical Inhibition Within the Primary Motor Cortex Can Be Modulated by Changing the Focus of Attention

It is well recognized that an external focus (EF) compared with an internal focus (IF) of attention improves motor learning and performance. Studies have indicated benefits in accuracy, balance, force production, jumping performance, movement speed, oxygen consumption, and fatiguing task. Although behavioral outcomes of using an EF strategy are well explored, the underlying neural mechanisms remain unknown. A recent TMS study compared the activity of the primary motor cortex (M1) between an EF and an IF. More precisely, this study showed that, when adopting an EF, the activity of intracortical inhibitory circuits is enhanced.
On the behavioral level, the present protocol tests the influence of attentional foci on the time to task failure (TTF) when performing submaximal contractions of the first dorsal interosseous (FDI). Additionally, the current paper describes two TMS protocols to assess the influence of attentional conditions on the activity of cortical inhibitory circuits within the M1. Thus, the present article describes how to use single-pulse TMS at intensities below the motor threshold (subTMS) and paired-pulse TMS, inducing short-interval intracortical inhibition (SICI) when applied to the M1. As these methods are assumed to reflect the responsiveness of GABAergic inhibitory neurons, without being affected by spinal reflex circuitries, they are well suited to measuring the activity of intracortical inhibitory circuits within the M1.
The results show that directing attention externally improves motor performance, as participants were able to prolong the time to task failure. Moreover, the results were accompanied by a larger subTMS-induced electromyography suppression and SICI when adopting an EF compared to an IF. As the level of cortical inhibition within the M1 was previously demonstrated to influence motor performance, the enhanced inhibition with an EF might contribute to the better movement efficiency observed in the behavioral task, indicated by a prolonged TTF with an EF.

The Influence of Attentional Foci on Motor Performance:
The behavioral tests in the current study were used to prove the feasibility of the motor task and to identify the subjects who reacted positively when applying an EF. In line with previous studies (see1 for a review), our results show a prolonged TTF when the participants adopted an EF compared to an IF (see Figure 3). Thu...

Using two different transcranial magnetic stimulation (TMS) protocols, this manuscript describes how to measure and compare cortical inhibition within the primary motor cortex when adopting different attentional foci.

It is well recognized that an external focus (EF) compared with an internal focus (IF) of attention improves motor learning and performance. Studies have ...

The overall goal of these two transcranial magnetic stimulation protocols is to investigate the activity of intracortical inhibitory circuits within the primary motor cortex or M1 while performing motor tasks under different attentional foci. Although many studies have established the advantage of an external compared to an internal focus of attention, little is known about the underlying neural mechanisms. Despite enhanced motor performance, an external focus of attention is usually accompanied by a decreased muscular activity, therefore we speculated that inhibitory mechanisms might be involved.The applied TMS methods, namely subTMS and SICI allow to better understand the impact of attentional foci on the activity of the inhibitory circuits within the primary motor cortex. The main advantage of the subthreshold transcranial magnetic stimulation technique is that there is no movement artifact due a low stimulation intensity. In contrast, the conventional paired-pulse protocol uses higher stimulation intensities and therefore leads to muscle contractions.However, this method is well-established and it's impact on the GABAeric sinuses is thoroughly investigated. Begin by having the participant sit in the testing chair and place a monitor one meter in front of them. Next, place the left arm in a comfortable and relaxed position under the table resting on the left leg.Place the right arm of the subject in a custom-belt splint in pronated position. Align the finger joint with the access of rotation of the custom-made device. Once the optimal position is found, take a picture of the anteroposterior and medial lateral positions of the splint to use comparable positions for each session in the experiment.Begin by aligning the axis of rotation of the goniometer and the metacarpophalangeal joint. Place the force transducer in a way that allows for maximum voluntary contractions. Then, ask the participant to perform three maximal isometric abductions of the index finger with a 30-second break between each contraction and determine the Fmax.Note the participant must push the lever against the force transducer without any instructions about the focus of attention. After maximal contractions, remove the force transducer allowing the index finger to move freely in the transverse plane. Then, fill a bottle of water to amount representing the 30%of Fmax and attach the weight of Fmax to the rope of the device.Have the participant hold the finger in the target position by counteracting the weight, performing an abduction of the index finger. Have them perform the task until task failure. Press the record button on the recording software to start recording the goniometer signal and wait until task failure.Once task failure is reached, press the stop recording button on the recording software to stop the recording and save the goniometer signal on the computer. Finally, remove the participant's hand from the orthopedic splint. Begin by placing the silver-silver chloride bipolar surface electrodes in a belly-tendon montage on the FDI muscle with one centimeter inter-electrode distance.Connect the EMG cable or FDI muscle and the goniometer cable to an EMG amplifier and to an AD converter. Finally, use the surface electrodes to record and measure muscular activity in electrophysiological responses elicited by brain stimulation from the FDI muscle. Begin by placing the reflective markers on the participant's forehead with double-sided adhesive tape.Use a figure-of-eight coil attached to a TMS stimulator to deliver stimuli to the contralateral motor area. Then, find the optimal position, or hot spot, of the coil relative to the skull for eliciting motor evoked potentials, MEPs, in the FDI muscle by performing a classical mapping procedure. To do this, place the coil approximately 0.5 centimeters anterior to the vertex and over the midline with the coil handle pointing at 45 degrees towards the contralateral forehead.Get the participant accustomed to the TMS stimuli by starting the intensities below 25%of maximum stimulator output, or MSO. Then, start to increase the stimulation intensity and move the coil in the medial lateral and rostro-frontal direction to discover the hot spot. Once the hot spot is found, record the optimal position with the neuro-navigation system.Determine the active motor threshold, or AMT, by adjusting the intensity of the stimulator output. Next, fill a bottle of water with the weight that represents 10%of Fmax. Ensure that the participant remains in a relaxed, comfortable position.Then, find the optimal intensity for eliciting subTMS-induced EMG suppression by successfully diminishing in steps of 2%MOS from the AMT determined previously. Then, have the participants perform a few practice trials in order to match the target force. Have the participant perform four separate isometric index finger abductions at 10%of Fmax and record the EMG signal of the FDI.Record 40 trials with, and 40 trials without TMS with randomized ISIs for each condition in a counterbalanced order. Use the same previously determined optimal stimulation intensity. The onset of subTMS EMG suppression is defined as the moment when the difference between the trials with and those without TMS is negative for at least four milliseconds in a time window from 20 to 50 milliseconds after the TMS.Finally, to conduct the paired pulse TMS, move the coil over to the hot spot at M1.Set the intensity on the stimulator, the ISI, at 2.5 milliseconds in the interval between paired and single-pulse TMS at 0.25 hertz. Finally, ask the participant to perform four separate isometric index finger abductions at 10%of Fmax and record the EMG signal of the FDI. During the isometric contraction, record 20 TMS stimuli for each condition in a counterbalanced order.The amount of short-interval intracortical inhibition is defined as the ratio between the control MEP single-pulse and the conditioned MEP paired-pulse. The TTF was prolonged when the participants adopted an external rather than an internal focus of attention. As subthreshold intensities are used, no muscle twitches induced by stimulation which may disturb motor performance.Results indicated that subTMS-induced EMG suppression was instantly enhanced when using an EF compared to an IF.Further, when adopting an EF, participants showed more short-interval intracortical inhibition. This is well in line with the subTMS results and suggests that GABAergic neurons constituting the intracortical inhibitory circuits are modulated differently within the M1 according to the type of attentional focus. Once mastered, this protocol can be done in approximately 90 minutes if it is performed properly.While attempting the subthreshold TMS procedure, it is important to set the right stimulation intensity to get the subTMS-induced EMG suppression in the FDI muscle. For this purpose, it is important to average at least 40 trials with stimulation and 40 trials without stimulation. In addition to subTMS and paired-pulse TMS protocols measuring intracortical inhibition within M1, other methods like the measurement of surround inhibition can be performed in order to reveal additional mechanisms that might be involved to increase task efficiency with an external compared to internal focus of attention.After watching this video, you should have a good understanding of how to apply subTMS and paired-pulse TMS over the primary motor cortex. These methods can be used in order to investigate the impact of different attentional foci on the activity of the primary motor cortex.

intracortical-inhibition-within-primary-motor-cortex-can-be-modulated

Research

JoVE Journal

Behavior

Transcranial magnetic stimulation (TMS) is a non-invasive tool to gain insight on the physiology and function of the human nervous system.  Here, we present our TMS techniques to study cortical excitability of the upper limb and lumbar musculature.

Utilizing Transcranial Magnetic Stimulation to Study the Human Neuromuscular System

Source: Kuhn, Y. et al. Intracortical Inhibition Within the Primary Motor Cortex Can Be Modulated by Changing the Focus of Attention. J. Vis. Exp. (2017)This video demonstrates the use of transcranial magnetic stimulation (TMS) to modulate motor neuron activity and measure muscle responses via electromyography (EMG). It outlines the steps for locating the motor hotspot, determining stimulation thresholds, and assessing the effects of subthreshold TMS (subTMS) on cortical inhibition.

Transcranial Magnetic Stimulation for Modulating Muscle Response in Humans

Single-pulse transcranial magnetic stimulation over the primary motor cortex, neuronavigation, and registration of electromyographic activity of hand muscles were used in this study to explore corticospinal excitability while participants were observing action sequences.

Corticospinal Excitability Modulation During Action Observation

This article aims to describe a basic protocol for combining transcranial direct current stimulation (tDCS) with proton magnetic resonance spectroscopy (1H-MRS) measurements to investigate the effects of bilateral stimulation on primary motor cortex metabolism.

The Use of Magnetic Resonance Spectroscopy as a Tool for the Measurement of Bi-hemispheric Transcranial Electric Stimulation Effects on Primary Motor Cortex Metabolism

Attention control comprises enhancement of target signals and attenuation of distractor signals. We describe an approach to measure separately but concurrently, the neurophysiology of attending and ignoring in sustained intermodal attention, utilizing a passive control condition during which neither process is continuously engaged.

Measurement of Neurophysiological Signals of Ignoring and Attending Processes in Attention Control

Controlling an identical movement with position or force feedback results in different neural activation and motor behavior. This protocol describes how to investigate behavioral changes by looking at neuromuscular fatigue and how to evaluate motor cortical (inhibitory) activity using subthreshold TMS with respect to the interpretation of augmented feedback.

Force and Position Control in Humans - The Role of Augmented Feedback

We describe an experimental procedure to quantify excitability and inhibition of primary motor cortex during a motor response inhibition task by using Transcranial Magnetic Stimulation throughout the course of a Stop Signal Task.

Online Transcranial Magnetic Stimulation Protocol for Measuring Cortical Physiology Associated with Response Inhibition

This article describes new approaches to measure and strengthen functionally specific neural pathways with transcranial magnetic stimulation. These advanced noninvasive brain stimulation methodologies can provide new opportunities for the understanding of brain-behavior relations and development of new therapies to treat brain disorders.

Measuring and Manipulating Functionally Specific Neural Pathways in the Human Motor System with Transcranial Magnetic Stimulation

We present a suite of standardized single- and paired-pulse transcranial magnetic stimulation (TMS) recording protocols, with options for conventional amplitude measurements and threshold-tracking. This program can control three different types of magnetic stimulators and is designed to enable all tests to be performed conveniently by a single operator.

Conventional and Threshold-Tracking Transcranial Magnetic Stimulation Tests for Single-handed Operation

Short-latency afferent inhibition (SAI) is a transcranial magnetic stimulation protocol to probe sensorimotor integration. This article describes how SAI can be used to study the convergent sensorimotor loops in the motor cortex during sensorimotor behavior.

Combined Peripheral Nerve Stimulation and Controllable Pulse Parameter Transcranial Magnetic Stimulation to Probe Sensorimotor Control and Learning

Learn how to use transcranial magnetic stimulation to investigate intracortical inhibition in the primary motor cortex during motor tasks with different attentional foci. This protocol reveals neural mechanisms underlying attention effects.

Intracortical Inhibition Within the Primary Motor Cortex Can Be Modulated by Changing the Focus of Attention

Explore More Videos